title: Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5- to 21-week-old rats.
abstract: OBJECTIVE
  The spontaneously hypertensive stroke-prone rat (SHRSP) is a potential animal model of human lacunar stroke, but there is little information on SHRSP small vessel pathology, especially in young rats. We investigated the structural changes that occur in cortical and subcortical vessels and adjacent tissue in SHRSP before, during and after the onset of hypertension.
  
  
  METHODS
  We examined brains from SHRSP and Wistar Kyoto rats (WKY) at 5, 16 and 21 weeks of age. Structural changes in small arterioles and adjacent tissue were studied using antibodies to investigate different components of the neurovascular unit. We quantified staining in three standard regions, at two coronal levels.
  
  
  RESULTS
  Immunostaining for claudin-5, a marker of endothelial tight junctions, was reduced in SHRSP at all ages compared to age-matched WKY controls. Smooth muscle actin, glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 were increased in SHRSP vs. WKY by 16 weeks. Additionally, 21-week-old WKY and SHRSP rats fed a high-salt diet showed differences in claudin-5, glial fibrillary acidic protein and matrix metalloproteinase 9 staining compared to those fed a normal diet.
  
  
  CONCLUSIONS
  Endothelial tight junction alterations of SHRSP rats from the earliest ages point towards increased susceptibility to blood-brain barrier dysfunction and stroke, which is exacerbated by salt loading. Salt loading may also damage the neurovascular unit in WKY controls.
authors.affiliation: Division of Clinical Neurosciences Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, UK.
authors.forename: E L
authors.initials: EL
authors.lastname: Bailey
authors.forename: J M
authors.initials: JM
authors.lastname: Wardlaw
authors.forename: D
authors.initials: D
authors.lastname: Graham
authors.forename: A F
authors.initials: AF
authors.lastname: Dominiczak
authors.forename: C L M
authors.initials: CL
authors.lastname: Sudlow
authors.forename: C
authors.initials: C
authors.lastname: Smith
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D059345:Cerebral Small Vessel Diseases / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000473:pathology* / Q000503:physiopathology; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017673:Sodium Chloride, Dietary; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology
chemical_list: D017673:Sodium Chloride, Dietary